Respiratory syncytial virus deficient in soluble G protein induced an increased proinflammatory response in human lung epithelial cells
Respiratory syncytial virus deficient in soluble G protein induced an increased proinflammatory response in human lung epithelial cells
复制标题
DOI：
10.1016/j.virol.2004.10.004
复制
发表时间：
2004-12-20
期刊：
影响因子：
3.7
通讯作者：
König, W
中科院分区：
文献类型：
--
作者：
Arnold, R;König, B;König, W
呼吸道合胞病毒（Respiratory syncytial virus，RSV）是世界范围内婴幼儿呼吸道最重要的病原体。RSV的G糖蛋白（称为附着蛋白）由RSV感染的肺上皮细胞以膜锚定（mG蛋白）和由上皮细胞分泌的可溶性形式（sG蛋白）产生。目前，sG蛋白在原发性RSV感染中的生物学作用仍然难以捉摸。因此，我们分析了感染野生型RSV（RSV-WT）或其分泌型G蛋白产生缺陷的自发突变体（RSV-DeltasG）的人肺上皮细胞（A549）的炎症反应。我们的数据表明，RSV-DeltasG，在RSV-WT相比，诱导增加细胞表面ICAM-1的表达A549细胞和增强释放的趋化因子IL-8和RANTES感染后20小时。增加的蛋白质表达模式分别与ICAM-1、IL-8和RANTES编码的增强的mRNA水平相关。此外，当与RSV-WT相比时，用RSV-DeltasG感染的上皮细胞显示出转录因子NF-κ B的更多增加的结合活性。相反，突变体RSV-DeltasG在A549细胞中的复制效率低于RSV-WT。我们的数据表明，RSV在持续感染的过程中，通过产生sG蛋白来减少由受感染的常驻肺上皮细胞演变的有害炎症反应，从而支持其自身的复制。(C)2004爱思唯尔公司All rights reserved.
Respiratory syncytial virus (RSV) is worldwide the single most important respiratory pathogen in infancy and early childhood. The G glycoprotein of RSV, named attachment protein, is produced by RSV-infected lung epithelial cells in both a membrane-anchored (mG protein) and a soluble form (sG protein) that is secreted by the epithelial cell. Currently, the biological role of the sG protein in primary RSV infection is still elusive. Therefore, we analyzed the inflammatory response of human lung epithelial cells (A549) infected either with wild-type RSV (RSV-WT) or a spontaneous mutant thereof deficient in the production of secreted G protein (RSV-DeltasG). Our data reveal that RSV-DeltasG, in comparison to RSV-WT, induced an increased cell surface expression of ICAM-1 on A549 cells and an enhanced release of the chemokines IL-8 and RANTES after 20 h postinfection. The increased protein expression pattern correlated with an enhanced mRNA level encoding for ICAM-1, IL-8, and RANTES, respectively. Furthermore, epithelial cells infected with RSV-DeltasG showed a more increased binding activity of the transcription factor NF-kappaB when compared to RSV-WT. In contrast, the mutant RSV-DeltasG replicated less efficiently in A549 cells than RSV-WT. Our data suggest that RSV, in the course of an ongoing infection, reduces by the production of sG protein the detrimental inflammatory response evolved by the infected resident lung epithelial cell and thereby supports its own replication. (C) 2004 Elsevier Inc. All rights reserved.